Please use this identifier to cite or link to this item: http://umt-ir.umt.edu.my:8080/handle/123456789/5490
Title: 14-Deoxy-11,12-Didehydroandrographolide Induces DDIT3-Dependent Endoplasmic Reticulum Stress-Mediated Autophagy In T-47D Breast Carcinoma Cells
Authors: Heng Kean, Tan
Tengku Sifzizul, Tengku Muhammad
Mei Lan, Tan
Issue Date: 2-Apr-2016
Publisher: Toxicology and Applied Pharmacology
Citation: Vol.300;55-69p.
Abstract: 14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse inmitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/ DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.
URI: http://hdl.handle.net/123456789/5490
Appears in Collections:Journal Articles



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